Roughly 70% of the human genome is transcribed into RNA and, in most of these RNAs, complex higher-order structures underlie or fundamentally affect critical biological processes. RNA structures are the targets of many antibiotics, and RNA structure should be further exploited in small-molecule drug discovery efforts. For example, structures in the genomes of RNA viruses like HIV and influenza are essential for viral replication and pathogenesis. Half of the single nucleotide polymorphisms that are most strongly associated with human diseases occur in non-coding regions and are likely associated with abnormal RNA structures. Many nucleic acid-based therapeutics - including clinically important antisense and siRNA approaches - only work when exceedingly rare, high affinity, and structurally accessible sites are targeted. The Weeks laboratory has developed a chemical probing strategy, called SHAPE-MaP, that accurately reports on RNA structure in physiologically relevant contexts. This technology enables nucleotide-resolution RNA structure analysis information to be read out by massively parallel sequencing. Although independent groups describe SHAPE as the gold standard of RNA structure analysis, in its current form, SHAPE-MaP represents a cutting-edge but research-grade technology. The long-term vision of Ribometrix is to make SHAPE-MaP a platform technology with applications in drug discovery, translational research, and basic biological discovery. In this work, we will conduct proof-of-concept studies to solve impediments to adoption of SHAPE-MaP by non-expert laboratories via two aims: (1) to create and experimentally validate diagnostic controls to enable efficient evaluation and troubleshooting of a prototype SHAPE-MaP RNA structure analysis pipeline by non-expert users and (2) to examine and optimize formulation of SHAPE reagents for consistent handling. Progress to Phase 2 will be justified by data showing that novice users are able to implement and diagnose RNA structure probing experiments using easily handled, long-lifetime reagents, consistent with quantitative benchmarks. In Phase 2, Ribometrix will automate the downstream computational steps required to fully interpret SHAPE-MaP experiments and will create complete industrialized reagent platforms for use by pharmaceutical and academic customers and collaborators. Successful development of a user-friendly SHAPE technology platform will enable researchers in all areas of biomedical science to perform robust, quantitative experiments that explore the fundamental role of RNA in biology and that facilitate creation of RNA-based and RNA-directed therapeutics.